Vandana Khungar

Safety and efficacy of current direct‐acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV‐TARGET study

Data outside of clinical trials with direct‐acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct‐acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct‐acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090‐1101).

Safety and Efficacy of Current DAA Regimens in Kidney and Liver Transplant Recipients with Hepatitis C: Results from the HCV-TARGET Study.

Data outside of clinical trials with direct‐acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct‐acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct‐acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090‐1101).

Nonalcoholic Fatty Liver Disease: Pathophysiology and Management.

Nonalcoholic fatty liver disease (NAFLD) is an important cause of morbidity and mortality worldwide and is rapidly becoming the leading cause of end-stage liver disease and liver transplant. With a prevalence of 30% in the United States, it has reached epidemic proportions. The clinical syndrome of NAFLD spans from bland steatosis to steatohepatitis, which can progress to fibrosis and cirrhosis. The pathogenesis includes the roles of hormones, nutritional and intestinal dysbiosis, insulin resistance, lipotoxicity, hepatic inflammation, and genes. Noninvasive testing and liver biopsy indications are reviewed. Approved and investigational therapies for NAFLD and nonalcoholic steatohepatitis are outlined in this article.

Liver Transplantation for Cholestatic Liver Diseases in Adults

Liver transplantation (LT) is an established lifesaving therapy for patients with cholestatic liver diseases, including primary cholestatic diseases, namely primary sclerosing cholangitis and primary biliary cirrhosis, as well as secondary forms of cholestatic liver disease, including those with cholestatic complications of LT needing a retransplant. Patients with cholestatic liver diseases can be transplanted for complications of end-stage liver disease or for disease-specific symptoms before the onset of end-stage liver disease. These patients should be regularly assessed. Patient survival after LT for cholestatic liver diseases is generally better than for other indications.

Diagnostic accuracy of hepatorenal index in the detection and grading of hepatic steatosis

The objectives of our study were to assess the accuracy of hepatorenal index (HRI) in detection and grading of hepatic steatosis and to evaluate various factors that can affect the HRI measurement.

Hepatopulmonary Syndrome and Portopulmonary Hypertension: Implications for Liver Transplantation

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) represent serious pulmonary complications of advanced liver diseases. Orthotopic liver transplantation (OLT) is capable of completely resolving the underlying abnormalities associated with HPS. On the other hand, post-OLT response in patients with PoPH is less predictable, although heavily influenced by pre-OLT mean pulmonary arterial pressure. It remains the case that the opportunity to reverse 2 potentially fatal organ dysfunctions in the liver and the lung make HPS and PoPH more than worthy for further clinical investigations.

Direct-Acting Antiviral Agents: Regimens for the Interferon Failure Patient.

Over the past few years, tremendous advances have been made in the treatment of hepatitis C with direct-acting antiviral agents (DAAs), allowing treatment options for patients who have failed prior treatment with interferon. In addition to interferons severe adverse effect profile, and the inability of many patients to tolerate it, prior interferon-containing regimens were not as effective in achieving sustained virologic response as emerging therapies. New DAAs have demonstrated higher rates of sustained virologic response, shorter duration of treatment, and improved adverse effect profile.

Exploring opportunities to prevent cirrhosis admissions in the emergency department: A multicenter multidisciplinary survey

Patients with cirrhosis have high admission and readmission rates, and it is estimated that a quarter are potentially preventable. Little data are available regarding nonmedical factors impacting triage decisions in this patient population. This study sought to explore such factors as well as to determine provider perspectives on low‐acuity clinical presentations to the emergency department, including ascites and hepatic encephalopathy. A survey was distributed in four liver transplant centers to both emergency medicine and hepatology providers, who included attending physicians, house staff, and advanced practitioners; 196 surveys were returned (estimated response rate 50.6%). Emergency medicine providers identified several influential nonmedical factors impacting inpatient triage decisions, including input from a hepatologist (77.7%), inadequate patient access to outpatient specialty care (68.6%), and patient need for diagnostic testing for a procedure (65.6%). When given patient‐based scenarios of low‐acuity cases, such as ascites requiring paracentesis, only 7.0% believed patients should be hospitalized while 48.9% said these patients would be hospitalized at their institution (P < 0.0001). For mild hepatic encephalopathy, the comparable numbers were 19.5% and 55.2%, respectively (P < 0.001). Several perceived barriers were cited for this discrepancy, including limited resources both in the outpatient setting and emergency department. Most providers believed that an emergency department observation unit protocol would influence triage toward an emergency department observation unit visit instead of inpatient admission for both ascites requiring large volume paracentesis (83.2%) and mild hepatic encephalopathy (79.4%). Conclusion: Many nonmedical factors that influence inpatient triage for patients with cirrhosis could be targeted for quality improvement initiatives. In some scenarios, providers are limited by resource availability, which results in triage to an inpatient admission even when they believe this is not the most appropriate disposition. (Hepatology Communications 2018;2:237‐244)

How to Incorporate Quality Improvement and Patient Safety Projects in Your Training

QI and PS training is an important aspect to integrate within GI fellowship. There are a variety of ways to incorporate these efforts, including modifying existing divisional and departmental resources, building new curricula, completing available online modules and courses, and obtaining degrees through the university. There are numerous opportunities for scholarship within QI which fellows should be encouraged to pursue. Engagement in QI and PS efforts will help provide a more formal methodology for fellows to improve upon the practice of gastroenterology in the future.

Characterizing the risk of false-positive hepatocellular carcinoma in recipients transplanted with T2 MELD exceptions.

Background Patients with hepatocellular carcinoma (HCC) can receive Model for End-Stage Liver Disease (MELD) exception points to increase waitlist priority for liver transplantation. This process does not require a biopsy and is based on radiologic criteria. However, imaging modalities are imperfect, and some will ultimately have no HCC on explant. Methods This was a retrospective cohort study using national explant pathology data from 2012 to 2015. False-positive HCC was defined as answering “no” to the question: “was evidence of HCC (viable or nonviable) found in the explant?” in patients with T2 MELD exceptions. Results Four thousand one hundred seventeen patients received T2 MELD exceptions, of which 245 (6%) had false-positive HCC. Maximal tumor diameter of 3 to 5 cm and serum &agr; fetoprotein (AFP) greater than 100 ng/mL at transplant yielded a 50% lower risk of false-positive HCC (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.27-0.73 and OR, 0.57; 95% CI, 0.37-0.88, respectively). Recipients with immune-mediated liver disease were twice as likely to have no HCC on explant (OR, 2.12; 95% CI, 1.18-3.83) and had a predicted probability of false positive HCC greater than 10% regardless of largest tumor size or AFP. Significant among-center variability in the rate of false-positive HCC was seen. Conclusions The risk of false-positive HCC is markedly higher in certain groups, such that biopsy may be warranted before T2 MELD exception point approval. Transplant centers with high false-positive HCC rates may benefit from greater oversight.